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Objective The literature regarding gonadoblastoma risk in exonic Wilms’ tumor suppressor gene (WT1) pathogenic variants is sparse. The aim of this study is to describe the phenotypic and genotypic characteristics of Asian–Indian patients with WT1 pathogenic variants and systematically review the literature on association of exonic WT1 pathogenic variants and gonadoblastoma. Design Combined retrospective–prospective analysis. Methods In this study, 46,XY DSD patients with WT1 pathogenic variants detected by clinical exome sequencing from a cohort of 150 index patients and their affected relatives were included. The PubMed database was searched for the literature on gonadoblastoma with exonic WT1 pathogenic variants. Results The prevalence of WT1 pathogenic variants among 46,XY DSD index patients was 2.7% (4/150). All the four patients had atypical genitalia and cryptorchidism. None of them had Wilms’ tumor till the last follow-up, whereas one patient had late-onset nephropathy. 11p13 deletion was present in one patient with aniridia. The family with p.Arg458Gln pathogenic variant had varied phenotypic spectrum of Frasier syndrome; two siblings had gonadoblastoma, one of them had growing teratoma syndrome (first to report with WT1). On literature review, of >100 exonic point pathogenic variants, only eight variants (p.Arg462Trp, p.Tyr177*, p.Arg434His, p.Met410Arg, p.Gln142*, p.Glu437Lys, p.Arg458*, and p.Arg458Gln) in WT1 were associated with gonadoblastoma in a total of 15 cases (including our two cases). Conclusions WT1 alterations account for 3% of 46,XY DSD patients in our cohort. 46,XY DSD patients harboring exonic WT1 pathogenic variants carry a small but definitive risk of gonadoblastoma; hence, these patients require a gonadoblastoma surveillance with a more stringent surveillance in those harboring a gonadoblastoma-associated variant.

Risk of metastatic disease in the cluster 2-related pheochromocytoma/paraganglioma (PPGL) is low. In MEN2 patients, identification of origin of metastases from pheochromocytoma (PCC) or medullary thyroid carcinoma (MTC) is challenging as both are of neuroendocrine origin. We aim to describe our experience and perform a systematic review to assess prevalence, demographics, biochemistry, diagnostic evaluation, management, and predictors of cluster 2-related metastatic PPGL. Retrospective analysis of 3 cases from our cohort and 43 cases from world literature was done. For calculation of prevalence, all reported patients (n = 3063) of cluster 2 were included. We found that the risk of metastasis in cluster 2-related PPGL was 2.6% (2% in RET, 5% in NF1, 4.8% in TMEM127 and 16.7% in MAX variation). In metastatic PCC in MEN2, median age was 39 years, bilateral tumors were present in 71% and median tumor size was 9.7 cm (range 4–19) with 43.5% mortality. All patients had a primary tumor size ≥4 cm. Origin of primary tumor was diagnosed by histopathology of metastatic lesion in 11 (57.9%), 131I-MIBG scan in 6 (31.6%), and selective venous sampling and CT in 1 (5.3%) patient each. In subgroup of neurofibromatosis 1 (NF1), median age was 46 years (range 14–59) with median tumor size 6 cm and 57% mortality. To conclude, the risk of metastatic disease in cluster 2-related PPGL is low, being especially high in tumors with size ≥4 cm and associated with high mortality. One-third patients of NF1 with metastatic PPGL had presented in second decade of life. Long-term studies are needed to formulate management recommendations.

The data on the congenital hyperinsulinism (CHI) in Asian Indian patients is limited. Diazoxide is often unavailable in India, which poses challenge in managing CHI. The study was aimed to present our experience with CHI with a special focus on the effectiveness and cost-effectiveness of octreotide long-acting release (OCT-LAR) among diazoxide-responsive CHI. The data of 14 index cases with CHI registered at our center were retrospectively analyzed. The diagnosis of CHI was based on elevated serum insulin (3.4–32.5 μIU/ml) and C-peptide (0.58–1.98 ng/ml) at the time of symptomatic hypoglycemia (BG≤41 mg/dl). Fourteen patients (13 males) presented at a median (range) age of 3 (1–270) days, seizures being the most common mode of presentation (78.6%). Ten patients were diazoxide-responsive, two were partially responsive, while two were unresponsive. Genetics was available for eight patients; ABCC8 (n=3, 1 novel) and HADH (n=2, both novel) were the most commonly mutated genes. OCT-LAR was offered to eight patients including four with diazoxide-responsive disease and was universally effective. We propose a cost-effective approach to use OCT-LAR in the management of CHI, which may also make it more cost-effective than diazoxide for diazoxide-responsive disease. Five of the 11 (45.5%) patients had evidence of neurological impairment; notably, two patients with HADH mutations had intellectual disability despite diazoxide-responsiveness. We report three novel mutations in CHI-associated genes. We demonstrate the effectiveness of and propose a cost-effective approach to use OCT-LAR in diazoxide-responsive CHI. Mutations in HADH may be associated with abnormal neurodevelopmental outcomes despite diazoxide-responsiveness.

POU1F1 mutations are prevalent in Indian CPHD cohorts. Genotype–phenotype correlation is not well-studied. To describe phenotypic and genotypic spectrum of POU1F1 mutations in our CPHD cohort and present systematic review as well as genotype–phenotype analysis of all mutation-positive cases reported in world literature. Retrospective study of POU1F1 mutation-positive patients from a western-Indian center. PRISMA guidelines based pubmed search of published literature of all mutation-positive patients. Our cohort had 15 POU1F1 mutation-positive patients (9 index, 6 relatives). All had severe GH, TSH and prolactin deficiencies (GHD, TSHD and PD). TSHD was diagnosed earliest followed by GHD (median ages: TSHD-6 months, GHD-3 years), while PD was more variable. Two sisters had central precocious puberty at 7 years of age. Pubic hair was deficient in all post-pubertal patients (females: P1-P2, males: P3-P4). Splice-site/intronic/frameshift mutations were most common, while missense/nonsense mutations were less frequent (33%). Review of world literature yielded 114 patients (82 index patients) from 58 studies. GHD was present in all patients. TSHD was spared in 12.5% and PD in 4.4% patients. Missense/nonsense mutations accounted for 75% of spectrum. Phenotype-genotype analysis revealed higher mean peak-GH levels (1.1 vs 0.2 ng/ml, p = 0.008) and lower prevalence of anterior-pituitary hypoplasia (63.6% vs 86.3%, p = 0.03) in patients with heterozygous than homozygous and compound heterozygous mutations. We present largest series of POU1F1 mutation-positive patients. Precocious puberty and defective pubarche are lesser-appreciated phenotypic features. Our mutation spectrum is different from that of world literature. Patients with heterozygous mutations have milder phenotype.

Introduction: The role of glucocorticoids in primary autoimmune hypophysitis (PAH) has been fraught with variability in regimens, leading to inconsistent outcomes in terms of anterior pituitary (AP) hormonal recovery. Hence, we aimed to compare the clinical, hormonal, and radiological outcomes of a standardized high-dose glucocorticoid therapy group (GTG) in PAH with a matched clinical observation group (COG). Methods: Thirty-nine retrospective patients with PAH evaluated and treated at a single center in western India from 1999 to 2019 with a median follow-up duration of 48 months were subdivided into the GTG (n = 18) and COG (n = 21) and compared for the outcomes. Results: Baseline demographic, hormonal, and radiological features matched between the groups, except pituitary height, which was significantly higher in GTG. Cortisol, thyroid, and gonadal axes were affected in 25 (64%), 22 (56%), and 21 (54%) patients, respectively, and central diabetes insipidus was seen in 7 (18%) patients. Panhypophysitis (PH) was the most common radiological subtype (n = 33, 84.6%). Resolution of mass effects was similar in both groups. Overall and complete AP hormonal recovery was significantly higher in the GTG than in the COG (12/14 [85.7%) vs. 6/14 [42.8%], p = 0.02; 10/14 [71.4%] vs. 1/14 [7.7%], p = 0.0007, respectively). Proportion of cases with empty sella were significantly higher in the COG (9/20 [45%] vs 1/17 [5.9%], p = 0.001). Among PH patients in the GTG (n = 17), we found duration from symptoms onset to treatment as the predictor of recovery. Conclusion: In a PH subtype-predominant PAH cohort, a standardized high-dose glucocorticoid regimen resulted in higher overall and complete AP hormonal recovery than that in the COG. Initiation of glucocorticoids in the early disease course may have been contributory.

Introduction: Radionuclide therapy is a promising treatment modality in metastatic pheochromocytoma/paraganglioma (PPGL). There is scarce data on 131I-metaiodobenzyl guanidine (131I-MIBG) therapy from the Indian subcontinent. Hence, we aim to study the safety and effectiveness of low-dose, low-specific activity (LSA) 131I-MIBG therapy in patients with symptomatic, metastatic PPGL. Methods: Clinical, hormonal, and radiological response parameters and side effects of LSA 131I-MIBG therapy in patients with symptomatic, metastatic PPGL were retrospectively reviewed. World health organizations’ (WHO) symptomatic, hormonal, and tumor response, and response evaluation criteria in solid tumors (RECIST1.1) criteria were used to assess the response. Results: Seventeen (PCC: 11, sympathetic PGL: 06) patients (15 with disease progression) received low-dose LSA 131I-MIBG therapy. Complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD) were 18% (3/17), 24% (4/17), 18% (3/17), and 41% (7/17), respectively, for WHO symptomatic response; 20% (2/10), 10% (1/10), 30% (3/10), and 40% (4/10), respectively, for WHO hormonal response; and 19% (3/16), 6% (1/16), 31% (5/16), and 44% (7/16), respectively for tumor response based on RECIST1.1. All patients with symptomatic PD and 50% (2/4) with hormonal PD had progression as per RECIST1.1 criteria. Side effects included thrombocytopenia, acute myeloid leukemia, mucoepidermoid carcinoma, and azoospermia in 6% (1/17) each. Conclusions: Our study reaffirms the modest efficacy and safety of low-dose, LSA 131I-MIBG therapy in patients with symptomatic, metastatic PPGL. Symptomatic, but not hormonal, progression after 131I-MIBG therapy correlates well with tumor progression and should be further evaluated with imaging. In resource-limited settings, anatomic imaging alone may be used to assess tumor response to 131I-MIBG therapy.

To study the effect of prior testosterone replacement therapy (TRT) on the spermatogenic response to combined gonadotropin therapy (CGT) in severe and partial phenotype congenital hypogonadotropic hypogonadism (CHH) patients.Retrospective cohort study.Tertiary care center.Patients of CHH without (n = 17) and with prior TRT (n = 18) were subdivided into severe and partial groups, based on mean testicular volume ≤ 3 cc and 3 cc respectively.Participants were treated with hMG at a dose of 75-150 U 3/week and gradually escalating doses of hCG until maximum dose (2000 U 3/week or 5000 U 2/week) or serum total testosterone of ≥ 3.5 ng/ml was reached.Final mean TV, trough serum testosterone (T), sperm concentration RESULTS: Thirty-five patients (20 severe, baseline mean TV of 3.6 ± 2.7 ml) were started on CGT at 24.8 ± 6.1 years. The median duration of prior TRT was 38 (IQR 10-63.75) months in the exposed group. After 33 ± 12 months, final mean TV was 8.9 ± 5.5 ml, 86% achieved serum testosterone 3.5 ng/ml and 70% achieved spermatogenesis [median 5 (0-12.6) million/ml]. Patients without prior TRT had significantly higher peak sperm count than those with prior- TRT (median 9 vs 0.05 million/ml, p = 0.004). This effect of prior TRT was more pronounced in severe phenotype patients (median 7 vs 0 million/ml, p = 0.01).Prior-TRT may interfere with spermatogenic response to CGT in CHH patients, especially in those with a severe phenotype.

Objectives Pediatric pheochromocytoma and paraganglioma (PPGL) are rare tumors with limited data on the diagnostic performance of 68Ga-DOTA(0)-Tyr(3)-octreotate positron emission tomography–computed tomography (68Ga-DOTATATE PET/CT). We have described our experience of 68Ga-DOTATATE PET/CT in overall and von Hippel Lindau (VHL)-associated pediatric PPGL and compared its sensitivity with that of 131I-meta-iodobenzyl-guanidine (131I-MIBG), 18F-fluorodeoxyglucose PET/CT (18F-FDG PET/CT), and contrast-enhanced CT (CECT). Methods Retrospective evaluation of consecutive PPGL patients (age: ≤20 years), who had undergone at least one functional imaging [131I-MIBG, 18F-FDG PET/CT, and/or 68Ga-DOTATATE PET/CT], was done. Composite of anatomical and all the performed functional imaging scans, image comparator (IC), was considered as the gold standard for sensitivity analysis. Results In a cohort of 32 patients (16 males, age at diagnosis: 16.4 ± 2.68 years), lesion-wise sensitivity of 68Ga-DOTATATE PET/CT (95%) was higher than that of both 18F-FDG-PET/CT (80%, p=0.027) and 131I-MIBG (65%, p=0.0004) for overall lesions, than that of 18F-FDG-PET/CT (100 vs. 67%, p=0.017) for primary PPG, and than that of 131I-MIBG (93 vs. 42%, p=0.0001) for metastases. In the VHL (n=14), subgroup, 68Ga-DOTATATE PET/CT had higher lesion-wise sensitivity (100%) compared to 18F-FDG PET/CT (74%, p=0.045) and 131I-MIBG (64%, p=0.0145). Conclusions In our pediatric PPGL cohort, overall lesion-wise sensitivity of 68Ga-DOTATATE PET/CT was higher than that of 18F–FDG PET/CT and 131I-MIBG scintigraphy. Hence, we recommend 68Ga-DOTATATE PET/CT as the preferred modality in pediatric PPGL. 68Ga-DOTATATE PET/CT may evolve as a preferred imaging modality for disease surveillance in VHL.

Regional variation in prevalence of genetic mutations in growth hormone deficiency (GHD) is known. Study phenotype and prevalence of mutations in GH1, GHRHR, POU1F1, PROP1 genes in GHD cohort. One hundred and two patients {Isolated GHD (IGHD): 79; combined pituitary hormone deficiency (CPHD): 23} with orthotopic posterior pituitary were included. Auxologic, hormonal and radiological details were studied. All four genes were analysed in IGHD patients. POU1F1 and PROP1 were studied in CPHD patients. Of 102, 19.6% were familial cases. Height SDS, mean (SD) was − 5.14 (1.63). Peak GH, median (range) was 0.47 ng/ml (0–6.59), 72.5% patients had anterior pituitary hypoplasia (APH). Twenty mutations (novel: 11) were found in 43.1% patients (n = 44, IGHD-36, CPHD-8). GHRHR mutations (n = 32, p.Glu72* = 24) were more common than GH1 mutations (n = 4) in IGHD cohort. POU1F1 mutations (n = 6) were more common than PROP1 mutations (n = 2) in CPHD cohort. With few exceptions, this prevalence pattern is contrary to most studies in world-literature. No patients with peak GH > 4 ng/ml had mutations, signifying it as negative predictor. While many parameters were significant on univariate analysis, only positive family history and lower median peak GH levels were significant predictors of mutations on multivariate analysis in IGHD patients. At variance with world literature, we found reverse predominance of GHRHR over GH1 mutations, POU1F1 over PROP1 mutations and predominance of GHRHR p.Glu72* mutations thus re-affirming the regional diversity in GHD genetics. We report positive and negative predictors of mutations in GHD.

Introduction: 177Lu-DOTATATE-based peptide receptor radionuclide therapy (PRRT) is a promising therapy for metastatic and/or inoperable pheochromocytoma and paraganglioma (PPGL). We aim to evaluate the efficacy and safety of and identify predictors of response to 177Lu-DOTATATE therapy in metastatic and/or inoperable PPGL. Methods: This retrospective study involved 15 patients of metastatic or unresectable PPGL, who received 177Lu-DOTATATE PRRT therapy. Clinical, biochemical (plasma-free normetanephrine), and radiological (anatomical and functional) responses were compared before and after the last therapy. Results: A total of 15 patients (4 PCC, 4 sPGL, 5 HNPGL, 1 PCC + sPGL, 1 HNPGL + sPGL) were included. The median duration of follow up was 27 (range: 11–62) months from the start of PRRT. Based on the RECIST (1.1) criteria, progressive disease was seen in three (20%), stable disease in eight (53%), partial response in one (7%), and minor response in three (20%) and controlled disease in 12 (80%). On linear regression analysis the presence of PGL (P= 0.044) and baseline SUVmax >21 (P < 0.0001) were significant positive predictors of early response to PRRT. Encouraging safety profiles were noted with no long term nephrotoxicity and hematotoxicity. Conclusion: 177Lu-DOTATATE therapy is an effective and safe modality of treatment for patients with metastatic/inoperable PPGL. Although it is not prudent to withhold PRRT in metastatic PPGL with baseline SUVmax < 21, baseline SUVmax >21 can be used to predict early response to PRRT.

The optimum imaging modality for the screening of multiple endocrine neoplasia type 1 (MEN1)-associated tumors is not well established. Here, we compare the performance of contrast-enhanced CT (CECT) versus 68Ga DOTA-NOC/TATE PET/CT in MEN1 patients. The retrospective case record study is conducted at a tertiary health-care center. Thirty-four patients, who have undergone both CECT and 68Ga DOTA-NOC/TATE PET, were included in the analysis. CECT had higher per-lesion sensitivity than 68Ga DOTA-NOC/TATE PET/CT for the detection of parathyroid lesions, (82.6% vs. 24.6%, P < 0.001). 68Ga DOTA-NOC/TATE PET/CT had higher per-lesion sensitivity than CECT for the detection of metastases (85% vs. 47.5%, P < 0.001) and gastrinomas (90% vs. 10%, P = 0.003). When combined use of the two imaging modalities is compared to CECT alone (63.7% vs. 93.1%, P = 0.00012) and 68Ga-DOTA-NOC/TATE PET/CT alone (74.1% vs. 93.1%, P = 0.0057), it provided significantly higher per-lesion sensitivity for the detection of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). 68Ga-DOTA-NOC/TATE PET was more sensitive for the detection of gastrinomas and metastases than CECT, whereas it was less sensitive for the detection of parathyroid lesions than CECT. The combined use of both the imaging modalities significantly increases the sensitivity for detection of GEP-NETs.

Rationale and introduction To evaluate the computerised tomography (CT) characteristics of phaeochromocytoma (PCC) that differentiate them from other non-benign adrenal masses such as adrenocortical carcinoma (ACC), primary adrenal lymphoma (PAL) and adrenal metastases (AM). Methods This retrospective study was conducted at a tertiary health care institute from Western India. Patients presented between January 2013 and August 2016 with histological diagnosis of PCC or other non-benign adrenal mass having adequate reviewable imaging data comprising all four CECT phases were included. Results The study cohort consisted of 72 adrenal masses from 66 patients (33 PCC, 22 ACC, 4 PAL, 13 AM). Unlike other masses, majority of PCC (25/33) showed peak enhancement in early arterial phase (EAP). PCC had significantly higher attenuation in EAP and early venous phase (EVP), and higher calculated percentage arterial enhancement (PAE) and percentage venous enhancement (PVE) than other adrenal masses (P Conclusion Peak enhancement in EAP, PAE value ≥100% and EAP attenuation ≥100 HU differentiate PCC from other malignant adrenal masses with high specificity.

Aims To find the prevalence and predictors of nonalcoholic fatty liver disease (NAFLD) in Asian Indian polycystic ovary syndrome (PCOS) women. Materials and methods This is a prospective, cross-sectional study conducted at a tertiary care hospital from South India. Sixty women fulfilling the Rotterdam (2003) criteria for PCOS were recruited for the study. All participants were evaluated with ultrasound abdomen for fatty liver and additional biochemical investigations including fasting plasma glucose, postprandial plasma glucose, serum insulin, lipid profile and liver function tests. Results The mean age of the study population was 24.06 ± 5.9 (range: 15–39) years. Oligomenorrhea, hirsutism and acne were present in 58 (96.7%), 37 (61.7%) and 33 (55%) women. Mean BMI of the study population was 29.5 ± 5.28 (range: 19.95 to 45.44) kg/m2. Fifty (83.3%) women were obese (BMI: ≥ 25 kg/m2). Twenty-three (38.3%) women with PCOS had NAFLD. Three women each had isolated elevation of alanine transaminase (ALT) and aspartate transaminases (AST) whereas three women had elevation of both. All women with elevated transaminases had NAFLD. By univariate analysis, factors associated with NAFLD were serum total cholesterol, serum insulin, HOMA-IR, hyperandrogenism, ALT and AST. On multiple regression analysis using linear regression, HOMA-IR and hyperandrogenemia were the only significant predictors of NAFLD. Conclusion Our study reports NAFLD in more than one third of Asian Indian women with PCOS. In addition to insulin resistance (HOMA-IR), hyperandrogenemia is an independent predictor of NAFLD in women with PCOS.

Background Vitamin D dependent rickets type 1 (VDDR1) is a rare disease due to pathogenic variants in 1-α hydroxylase gene. We describe our experience with systematic review of world literature to describe phenotype and genotype. Methods Seven patients from six unrelated families with genetically proven VDDR1 from our cohort and 165 probands from systematic review were analyzed retrospectively. The clinical features, biochemistry, genetics, management, and long-term outcome were retrieved. Results In our cohort, the median age at presentation and diagnosis was 11(4–18) and 40(30–240) months. The delayed diagnoses were due to misdiagnoses as renal tubular acidosis and hypophosphatemic rickets. Four had hypocalcemic seizures in infancy whereas all had rickets by 2 years. All patients had biochemical response to calcitriol, however two patients diagnosed post-puberty had persistent deformity. Genetic analysis revealed two novel (p.Met260Arg, p.Arg453Leu) and a recurring variant (p.Phe443Profs*24). Systematic review showed that seizures as most common presentation in infancy, whereas delayed motor milestones and deformities after infancy. Diagnosis was delayed in 27 patients. Patients with unsatisfactory response despite compliance were >12 years at treatment initiation. Inappropriately normal 1,25(OH)2D may be present, however suppressed ratio of 1,25(OH)2 D/25(OH)D may provide a clue to diagnosis. Various region specific and hot-spot recurrent variants are described. Patients with truncating variants had higher daily calcitriol requirement and greatly suppressed ratio of 1,25(OH)2D/25(OH)D. Conclusion Delayed diagnosis may lead to permanent short stature and deformities. Truncating variants tend to have severe disease as compared to non-truncating variants. Diagnostic accuracy of 1,25(OH)2 D/25(OH)D ratio needs further validation.

Context Preoperative blockade with α-blockers is recommended in patients with pheochromocytoma/paraganglioma (PPGL). The data on calcium channel blockade (CCB) in PPGL are scarce. Objective We aimed to compare the efficacy of CCB and α-blockers on intraoperative hemodynamic instability (HDI) in PPGL. Methods In the interim analysis of this monocentric, pilot, open-label, randomized controlled trial, patients with solitary, secretory, and nonmetastatic PPGL were randomized to oral prazosin gastrointestinal therapeutic system (GITS) (maximum 30 mg, n = 9) or amlodipine (maximum 20 mg, n = 11). The primary outcomes were the episodes and duration of hypertension (systolic blood pressure ≥ 160 mmHg) and hypotension (mean arterial pressure Results The median (IQR) episodes (2 [1-3] vs 0 [0-1]; P = 0.002) and duration of hypertension (19 [14-42] vs 0 [0-3] minutes; P = 0.001) and intraoperative HDI duration (22.85 ± 18.4% vs 2.44 ± 2.4%; CI, 8.68-32.14%; P 0.002) were significantly higher in the prazosin GITS arm than the amlodipine arm, whereas episodes and duration of hypotension did not differ between the 2 groups. There was no perioperative mortality. One patient had intraoperative ST depression on the electrocardiogram. The drug-related adverse effects were pedal edema (1 in amlodipine), dizziness (1 in prazosin GITS), and tachycardia (6 in prazosin GITS and 3 in amlodipine). Conclusion Preoperative blockade with amlodipine is an efficacious alternative to prazosin GITS in preventing intraoperative HDI in PPGL. Larger studies that compare preoperative blockade by amlodipine with other α-blockers like phenoxybenzamine and/or doxazosin in PPGL patients are warranted.

Objective To report clinical, hormonal and structural effects of CYP11B1 pathogenic variations in Indian patients with 11β-hydroxylase deficiency (11βOHD) and find hormonal criteria that accurately distinguish 11βOHD from 21α-hydroxylase deficiency (21OHD). Design Retrospective record review of genetically diagnosed patients with 11βOHD. Patients and measurements Clinical features, hormonal parameters at diagnosis (by immunoassay) and recent follow-up of 13 genetically proven 11βOHD patients managed at our centre were retrospectively reviewed. ACTH-stimulated serum adrenal steroids (measured by LC-MS/MS) of 11βOHD were compared with those of simple virilizing and non-classic 21OHD. Structural analysis of the observed pathogenic variations was performed by computational modelling. Results Nine (four females) and four (all females) patients had classic and non-classic disease, respectively. All 11βOHD patients had elevated ACTH-stimulated serum 11-deoxycortisol (26.5-342.7 nmol/L) whereas none had elevated serum 17-hydroxyprogesterone (4.2-21.2 nmol/L); both hormonal parameters distinguished 11βOHD from 21OHD with 100% accuracy. ACTH-stimulated serum cortisol, but not 11-deoxycortisol, clearly distinguished classic ( 160 nmol/L) disease. Thirteen (eight novel, two recurrent) pathogenic variants were observed. Only missense mutations were observed among patients with non-classic disease. Computational modelling predicted the possible affection of enzyme structure and function for all the observed missense mutations. Conclusions This first Indian study describes 13 11βOHD patients, including four with the rarer non-classic variant. A total of eight novel pathogenic variants were identified in our study, highlighting regional genetic heterogeneity. Measurement of ACTH-stimulated adrenal steroids by LC-MS/MS will help avoid the misdiagnosis of 11βOHD as 21OHD and has potential to distinguish classic from non-classic 11βOHD.

The data from the Indian subcontinent on Medullary thyroid carcinoma (MTC) and associated endocrinopathies in hereditary MTC (HMTC) syndromes are limited. Hence, we analyzed clinical and biochemical characteristics, management, and outcomes of HMTC and other associated endocrinopathies [Pheochromocytoma (PCC) and Primary hyperparathyroidism (PHPT)] and compared with apparently sporadic MTC. The records of 97 (51 sporadic and 46 hereditary) consecutive MTC patients were retrospectively analyzed. RET mutation was available in 38 HMTC patients. HMTC group was subclassified into Multiple endocrine neoplasia (MEN) 2A index (n = 25), MEN2B index (n = 8), and MEN2A detected by familial screening (n = 12). Patients with HMTC and MEN2B index were younger at presentation than sporadic MTC. MEN2A patients detected by familial screening, but not MEN2A index and MEN2B index patients, had significantly lower serum calcitonin, smaller thyroid nodule size, more frequent early stage presentation (AJCC Stage ≤ II), and higher cure rate than sporadic MTC, which emphasizes the need for early diagnosis. RET (REarranged during Transfection) 634 mutations were the most common cause of HMTC and more frequently associated with PCC (overall 54% and 100% in those aged ≥ 35 years). Patients in ATA-Highest (HST) group had a universal presentation in stage IV with no cure. In contrast, the cure rate and postoperative disease progression (calcitonin doubling time) were similar between ATA-High (H) and ATA- Moderate (MOD) groups, suggesting the need for similar follow-up strategies for the latter two groups. Increased awareness of endocrine (PCC/PHPT) and non endocrine components may facilitate early diagnosis and management.

Mislabeling of T12 vertebra as L1 has been shown to reduce L1-L4 bone mineral density (BMD). However, the effect of such mislabeling on the L1-L4 BMD and prevalence of osteoporosis and/or osteopenia in a clinical setting is not known. The study aimed to the effect of mislabelling of T12 as L1 on the L1-L4 BMD and diagnosis of osteoporosis and/or osteopenia. It is a retrospective study done at a tertiary health care center in South India. Database of dual X-ray absorptiometry machine at our center was reviewed and BMD data of men aged more than 50 years and postmenopausal women who underwent BMD during the last 3.5 years were included in the analysis. A total of 570 subjects had undergone BMD testing at the lumbar spine of whom images of the T12 and lower part of the T11 were available for 293 subjects. Six of these with ≤1 eligible vertebra for the calculation of L1-L4 BMD were further excluded from the analysis. The BMD data of the remaining 287 subjects were noted. Later T12 was labeled as L1 and a new set of BMD data was obtained. Using the WHO classification, BMD status was classified as normal BMD, osteopenia, and osteoporosis for both the analyses. L1-L4 BMD (0.916 ± 0.163 vs 0.937 ± 0.170, p0.0001) and T-scores of L1-L4 (-2.23 ± 1.37 vs -2.06 ± 1.43, p0.0001) with mislabeling were significantly lower than those measured with correct labeling. BMD status was misclassified by T12 mislabelling as L1 in a total of 30 (10.4%) individuals. Inter-rater agreement between the 2 scenarios for the diagnosis of osteoporosis, osteopenia, and normal BMD was substantial (weighted Kappa: 0.87 [95%CI: 0.83-0.91]). To conclude, mislabeling of T12 as L1 significantly reduces L1-L4 BMD. However, the diagnosis of BMD status by mislabeling has a substantial agreement with that obtained with correct labeling.

Context Data are limited regarding prevalence, predictors, and mechanisms of persistent hypogonadotropic hypogonadism (HH) in males with a macroprolactinoma who achieve normoprolactinemia on dopamine-agonist therapy. None of the previous studies provide cutoffs to predict the achievement of eugonadism. Objective The objective of this work is to evaluate the prevalence of persistent HH and its determinants in men with a macroprolactinoma who achieve normoprolactinemia on cabergoline monotherapy. Design and Setting This retrospective study with prospective cross-sectional evaluation took place at a tertiary health care center. Patients Study participants included men with a macroprolactinoma and baseline HH who achieved normoprolactinemia on cabergoline monotherapy. Main Outcome Measures Outcome measures of this study included the prevalence of persistent HH and its predictors. Results Thirty participants (age, 38.3 ± 10.1 years) with baseline tumor size of 4.08 ± 1.48 cm and median (interquartile range) prolactin of 2871 ng/mL (range, 1665-8425 ng/mL) were included. Eight of 30 participants achieved eugonadism after a median follow-up of 3 years. Patients with persistent HH had suppression of the luteinizing hormone (LH)-testosterone axis with sparing of other anterior pituitary hormonal axes, including follicle-stimulating hormone-inhibin B. Baseline prolactin (1674 vs 4120 ng/mL; P = .008) and maximal tumor diameter (2.55 ± 0.36 vs 4.64 ± 1.32 cm; P = .003) were lower in patients who achieved eugonadism. Baseline maximal tumor diameter less than or equal to 3.2 cm (sensitivity: 75%, specificity: 63.6%) and serum prolactin less than or equal to 2098 ng/mL (sensitivity: 87.5%, specificity: 77.3%) best predicted reversal of HH. Conclusion Recovery of the LH-testosterone axis occurred in 26.7% of men with a macroprolactinoma who achieved normoprolactinemia on cabergoline monotherapy. Higher baseline tumor size and serum prolactin predict persistent HH. Our data favor chronic functional modification of the hypothalamic-pituitary-gonadal axis over gonadotroph damage as the cause of persistent HH.

Background: Recent increase in the non-specific use of prokinetics in clinical practice may alter the etiological profile of hyperprolactinemia and galactorrhea. Hence, we have studied the etiological profile of patients presenting with galactorrhea and characteristics of drug-induced galactorrhea. Materials and Methods: This retrospective study was conducted at a tertiary health care center from South India. Patients who presented with or referred for galactorrhea and/or hyperprolactinemia to the Department of Endocrinology between January 2017 and December 2017 were included in the study. Results: Forty women presented with or referred for galactorrhea to the Department of Endocrinology during the study period. Thirty-two patients had received drugs that are associated with hyperprolactinemia (levosulpiride in 15, domperidone in 13, ranitidine in 2, oral contraceptive pill in 1, and amisulpiride in 1) of whom etiology was proved in 27 patients, whereas in four patients the cause was inconclusive due to lack of follow-up. The patient on amisulpiride was found to have concomitant pituitary microadenoma. Idiopathic galactorrhea (n = 2), idiopathic hyperprolactinemia (n = 2), and prolactinoma (n = 4) accounted for the remaining cases. Six patients with prokinetic-induced galactorrhea had received cabergoline inspite of which hyperprolactinemia and/or galactorrhea persisted and six patients had also undergone pituitary magnetic resonance imaging (MRI) for evaluation of galactorrhea. Conclusions: Prokinetic use is the most common cause of galactorrhea in our study and often was investigated with costly tests and treated with D2 agonists unnecessarily. Hence, there is a need to ensure measures to reduce the non-specific use of prokinetics and increase awareness regarding the occurrence of galactorrhea with prokinetics use, to reduce unnecessary investigations and treatment.

Background: Preoperative blockade with α-blockers is recommended in patients with pheochromocytoma/paraganglioma (PPGL). The data on calcium channel blockade (CCB) in PPGL is scarce. We aim to compare the efficacy of CCB and α-blockers on intraoperative haemodynamic instability (HDI) in PPGL. Methods: In the interim analysis of this monocentric, pilot, open-label, randomized controlled trial, patients with solitary, secretory, and nonmetastatic PPGL were randomized to oral prazosin (maximum 30mg, n=9) or amlodipine (maximum 20mg, n=11). The primary outcomes were the episodes and duration of hypertension (SBP≥160mmHg) and hypotension (MAP

The data in genotype-phenotype correlation in Indian von Hippel-Lindau (VHL) patients is limited. We have retrospectively studied 31 genetically proven VHL patients with pheochromocytoma/paraganglioma (PCC/PGL) from families and have reviewed the World literature on PCC/PGL in patients with large VHL deletions. Three patients had large deletions and 28 patients had other mutations [missense mutations in 25, 3 bp deletion in 2 and single bp duplication in one]. Unilateral PCC were significantly more common in patients with large VHL deletions whereas multiple PCC (bilateral PCC or PCC + sympathetic PGL) were significantly more common in those with other mutations. World literature review confirmed the rarity of PCC/PGL in patients with large deletions and we report the first definitive case of PCC associated with complete VHL deletion. Pancreatic neuroendocrine tumours were more common, often metastatic and the most common cause of death in our cohort. Our study had eight parent off-spring pairs from five families. The off-springs were significantly younger at presentation and had significantly higher number of PCC/PGL. In conclusion, PCC/PGL are rare in patients with large VHL deletions and if occur are most likely to be solitary. Patients with bilateral PCC or multifocal PCC/PGL are least likely to have large VHL deletions. Our study also provides additional evidence for existence of the phenomenon of anticipation in VHL syndrome.

Objective To study genotype–phenotype spectrum of triple A syndrome (TAS). Methods Retrospective chart analysis of Indian TAS patients (cohort 1, n = 8) and review of genotyped TAS cases reported in world literature (cohort 2, n = 133, 68 publications). Results Median age at presentation was 4.75 years (range: 4–10) and 5 years (range: 1–42) for cohorts 1 and 2, respectively. Alacrima, adrenal insufficiency (AI), achalasia and neurological dysfunction (ND) were seen in 8/8, 8/8, 7/8 and 4/8 patients in cohort 1, and in 99, 91, 93 and 79% patients in cohort 2, respectively. In both cohorts, alacrima was present since birth while AI and achalasia manifested before ND. Mineralocorticoid deficiency (MC) was uncommon (absent in cohort 1, 12.5% in cohort 2). In cohort 1, splice-site mutation in exon 1 (p.G14Vfs*45) was commonest, followed by a deletion in exon 8 (p.S255Vfs*36). Out of 65 mutations in cohort 2, 14 were recurrent and five exhibited regional clustering. AI was more prevalent, more often a presenting feature, and was diagnosed at younger age in T group (those with truncating mutations) as compared to NT (non-truncating mutations) group. ND was more prevalent, more common a presenting feature, with later age at onset in NT as compared to T group. Conclusion Clinical profile of our patients is similar to that of patients worldwide. Alacrima is the earliest and most consistent finding. MC deficiency is uncommon. Some recurrent mutations show regional clustering. p.G14Vfs*45 and p.S255Vfs*36 account for majority of AAAS mutations in our cohort. Phenotype of T group differs from that of NT group and merits future research.

Introduction Although few studies have demonstrated utility of 18F- fluoro-2-deoxy-d-glucose positron emission tomography/computerised tomography (18F-FDG PET/CT) in benign pheochromocytoma/paragangliomas (PCC/PGLs), there limited data on factors predicting the FDG uptake in PCC/PGL. Methods The study was conducted at a tertiary health care centre. In addition to the routine investigations, all patients (n = 96) with PCC/PGL were evaluated with 18F-FDGPET/CT and majority (n = 78) underwent 131I-metaiodobenzyl guanidine (131I-MIBG) scintigraphy. Forty-three patients also underwent testing for germline mutations in five PCC/PGL susceptibility genes (VHL, RET, SDHB, SDHC and SDHD) and all patients were evaluated clinically for neurofibromatosis-1. Results The study included 96 patients with PCC/PGL(82 benign and 14 malignant). FDGSUVmax was significantly higher for malignant than benign PCC/PGL(P = 0.009) and for extra-adrenal PGL than adrenal PCC (P = 0.017). In subgroup analysis, metanephrine-secreting PCC and non-secretory PCC had significantly lower FDG SUVmax than normetanephrine-secreting PCC (P = 0.017, P = 0.038 respectively), normetanephrine-secreting-sympathetic PGL (P = 0.008, P = 0.019 respectively) and non-secretory sympathetic PGL (P = 0.003, P = 0.009 respectively). Patients with mutations in cluster 1 genes (n = 14) had significantly higher FDG SUVmax than those with mutations in cluster 2 genes (n = 4) (P = 0.04). Sensitivities of 131I-MIBG and 18F-FDG PET/CTwere 77.78% and 100% for cluster 1 genes-related PCC/PGL whereas they were 100% and 50% for cluster 2 genes-related PCC/PGL, respectively. Multivariate regression analysis of mutation positive patients identified genetic status as the only independent predictor of FDG SUVmax. Conclusion The study suggests that the underlying genetic status determines FDG uptake in PCC/PGL and not location, secretory status or malignancy.

The "rule of 10" used to describe pheochromocytoma/paragangliomas (PCC/PGLs) has been challenged. However, recent studies suggested that pediatric PCC/PGLs may follow a pattern. Hence, we reviewed the available literature to verify the same. We searched PubMed, Scopus, ProQuest, and Google Scholar for studies describing the genotype and/or phenotype characteristics of pediatric PCC/PGL cohorts published after 2000 in English language and those with sample size more than 35 were included in this review. Pediatric PCC/PGLs were malignant in 10%, synchronous bilateral in 20%, extra-adrenal in 30%, among which, 30% were extra-abdominal and familial in 40%. PCC/PGL diagnosed during pediatric age recurs in 50% by 30 years of follow-up and 60% cases occur in boys. Seventy percent of children with PCC/PGL are likely to have sustained hypertension. Germline mutations could be identified in 80% of children with PCC/PGL and 90% are secretory. The review concludes that pediatric PCC/PGLs follow a pattern, which we call "10%-90% rule." This new rule will help easily remember the characteristics of pediatric PCC/PGLs.

Aims: There are variable reports on the reversibility of type 2 diabetes mellitus (type 2 DM) with higher rates among younger patients with short duration of diabetes. Hence, we studied the reversibility of diabetes among young adults with newly diagnosed type 2 DM. Methods: This prospective study included 32 patients with newly diagnosed type 2 DM. All type 2 DM patients were initially treated with intensive lifestyle therapy (ILT) (low-calorie diet [1500 kcal/day] and brisk walking for 1 h/day]). Four patients who with HbA1C

Hypocalcemia is one of the sequelae following thyroidectomy (TT) and becomes a complication when it becomes permanent. Parathyroid preservation is a crucial step in the skillful operative procedure of TT. When due care is not taken, the surgeon and the treating physician are faced with the issue of treating the dreaded complication of permanent hypocalcemia. In this article, we address the issue of hypocalcemia following thyroid surgery and its management. How to cite this article Kolly A, Sarathi V, Bothra S, Chekavar A, Sabaretnam M, Agarwal A. Hypocalcemia: What a Surgeon should know. World J Endoc Surg 2017;9(2):72-77.

Background and aims To study the prevalence of thyroid disorders and their association with microvascular complications among adult type 2 diabetes mellitus (T2DM) patients from south-coastal Andhra Pradesh, India Methods This cross-sectional study included 500 subjects with T2DM and was conducted in a tertiary health care center from south-coastal Andhra Pradesh. Participants previously diagnosed with thyroid disorders were excluded from the study. Results Thyroid dysfunction was observed in 98 (19.6%) subjects of which subclinical hypothyroidism (n = 66, 13.2%) was the most common. Subclinical hypothyroidism (SCH) was more frequent in obese patients (16.2% vs 7.6%, p = 0.007) and metformin users (9.6% vs 18.7%, p = 0.0044). Diabetic retinopathy (27.3% vs 8.9%, p = 0.001) was significantly more frequent in SCH patients than euthyroid T2DM patients. Conclusion Among T2DM patients from south-coastal Andhra Pradesh the prevalence of thyroid dysfunction, especially that of SCH was high; SCH was more frequent among obese and nonmetformin users and was associated was associated with increased risk of diabetic retinopathy.

Defects in the initial steps of steroidogenesis usually present with female external genitalia in both 46,XX and 46,XY. Hence, they are not often considered in the differential diagnosis of primary adrenal insufficiency children with normal male external genitalia. Here, we report a boy with normal male external genitalia who presented with hyperpigmentation since the age of 2 years but diagnosis was delayed till 11 years of age. Evaluation revealed low-serum cortisol with elevated adrenocorticotropic hormone and direct renin level confirming primary adrenal insufficiency. Clinical exome sequencing analysis revealed a homozygous c.1351C>T (p.R451W) mutation in exon 8 of the CYP11A1 gene which was confirmed on Sanger sequencing. Both parents were heterozygous for the variation. To conclude, we report the first case of CYP11A1 deficiency from India. The report reiterates the existence of non-classic CYP11A1 deficiency characterised by primary adrenal insufficiency and normal male external genitalia in 46,XY.

Context Conventional fractionated radiotherapy (CRT) achieves control of pathological hypercortisolism in 75%-80% of patients with persistent or recurrent Cushing's disease (CD), over a mean period of 18-24 months. Medical therapy is recommended as bridge therapy while awaiting RT effect. Objective To determine long-term outcome of CRT and its predictors in CD patients. Design, setting and patients This is a retrospective case record analysis of 42 patients with CD who received CRT as a treatment modality and had at least 12 months post-RT follow-up. The dose delivered was 45 Gy in 25 fractions over 5 weeks. Demographic details, hormonal evaluation and radiological data were extracted from case records. Dexamethasone suppressed cortisol at cut-off of 1.8 µg/dL was used to define remission or recurrence. Possible predictors for remission and recurrence were analysed. Results The mean age at the time of CRT administration was 23.7 ± 10.7 (range: 12-48) years. A total of 29 (69%) patients achieved remission 26.5 ± 28.5 (median: 18, range: 3-120) months after RT, while 13 (31%) patients had persistent disease at last follow-up. There were no significant predictors of disease remission after CRT. Six (20.7%) patients had recurrence after a documented initial remission. Recurrence occurred 66.6 ± 25.9 (median: 74; range: 18 to 90) months after documented remission. Recurrence of the disease was exclusively seen in patients who received peri-RT cabergoline. Peri-CRT use of cabergoline was significantly associated with increased recurrence rates (P = .016). Conclusion Use of cabergoline in the peri-CRT period did not affect initial remission after CRT but was associated with increased recurrence after initial remission in CD.

Background Type 1 diabetes mellitus (T1DM) is an autoimmune disease, characterized by loss of insulin-producing beta cells of the islets of Langerhans in the pancreas, causing insulin deficiency. Celiac disease (CD) has been seen in 3 to 8% of T1DM patients. Celiac disease is characterized by impaired immunological response to ingested gluten. Gluten consumption might be a shared causative factor for the development of T1DM and CD. Celiac crisis is a life-threatening condition in which CD causes acute dramatic metabolic dysregulation. Methods A 52-year old lady with a 10-year history of type 1 diabetes mellitus presented with 2-months history of diarrhea associated with loss of appetite, nausea, pain abdomen, and weight loss of 13 kg. Initial laboratory findings revealed hyperglycemia, metabolic acidosis with hyperchloremia, hypokalemia, hypocalcemia, and hypoalbuminemia. She also had iron and folate deficiency. Haemoglobin level was 9.4 g/dl. HIV status and viral hepatitis serology were negative, and stool examination did not suggest an infectious etiology. For evaluation of diarrhea, serological blood test for celiac disease was done; antiendomysium antibodies of the immunoglobulin A (anti EA IgA) was 158.7 U/ml (normal: 0–20 U/ml), tissue transglutaminases of immunoglobulin A (tTGA IgA) was >200 U/ml (normal: 0–20 U/ml). Histological findings of duodenal biopsy post endoscopy were consistent with celiac disease grade 3 according to the Marshal classification. After the introduction of the gluten-free diet, she gained weight, her metabolic abnormalities resolved with better glycemic control. Results After excluding other reasons of acute diarrhea and based on the patient‘s findings including metabolic acidosis, hypoproteinemia, hypocalcemia, hypokalemia and weight loss of 13 kg, our patient was diagnosed with celiac crisis. Advising a gluten-free diet results in prompt and dramatic improvement in the patient‘s symptoms. Conclusions In the literature, celiac crisis in adults have rarely been notified, and for this reason, celiac disease rarely is considered in adults presenting with acute severe diarrheal illness, even when infectious etiologies have been excluded. A type 1 diabetic patient who presents with severe unexplained diarrhea and malabsorption should be tested for celiac disease.

Background: Steroid 11β-hydroxylase (CYP11B1) deficiency (11βOHD) is the second most common form of congenital adrenal hyperplasia (CAH). CAH is more likely to be missed in boys, particularly in patients with 11βOHD. Here, we report two boys with 11βOHD who presented late and the consequences of late diagnosis in them. Case presentation: Case 1: A-4-year-old boy presented with acne, appearance of axillary and pubic hair since the age of 3 years. Examination revealed tall stature (height z score: 4.6; predicted adult height 5000 ng/dl) and deoxycortisol (>1000 ng/dl). 17OHP was slightly elevated (334.73 ng/dl). Ultrasound scrotum revealed the presence of testicular adrenal rests (TARTs) in both testes. He had grade 1 hypertensive retinal changes and concentric left ventricular hypertrophy. Case 2: A-12-year-old presented with hypertensive encephalopathy. On examination he had normal stature for age (height: 138 cm; ≈predicted adult height =short), P4, G4 (stretched phallic length: 9 cm) and nodular testes measuring 4 cc on right and 6 cc on left. His bone age was 18 years and serum potassium was 2.67 mEq/L. Serum total testosterone was 229.77 ng/dl but LH was suppressed (0.03 mIU/ml). Serum 8:00 am cortisol level was low (0.39 µg/dl) with markedly elevated corticosterone levels (>5000 ng/dl) and deoxycortisol (>2000 ng/dl). 17OHP was slightly elevated (239.3 ng/dl). Ultrasound scrotum revealed bilateral TARTs. He had grade 1 hypertensive retinal changes and mild concentric left ventricular hypertrophy. Conclusion: Late diagnosis is common in boys with classic 11βOHD. It leads to disastrous complications such as hypertensive encephalopathy and/or hypertensive end organ damage, significantly compromises adult height potential and may have adverse impact on future fertility. Hence, early diagnosis of 11βOHD is essential.

Background: Sometimes peripheral precocious puberty (PPP) is the underlying cause of central precocious puberty (CPP) and is called as secondary CPP. In most of the secondary CPP, the role of the PPP is evident at diagnosis of CPP. Here we report a case of secondary CPP who was initially misdiagnosed as idiopathic CPP. Case presentation A-6.25-years-old boy, born of a third degree consanguineous consummation, presented with appearance of pubic hair and enlargement of phallus since the age of 4 years. He has history of mild global developmental delay, predominantly affecting language milestones. There was no family history of early puberty, sibling deaths or ambiguous genitalia. His height was 113 cm (-0.54 SDS ) and mid-parental height was 176.5 (+0.31 SD), Sexual maturity rating was P3, G3 (stretched phallic length: 6 cm) and bilateral testes measuring 5 cc each. He had multiple large café-au-lait spots over the lower extremities with irregular borders. Bone age was 9.5 years. Serum testosterone was elevated (190.1 ng/dl) with LH of 0.31 mIU/ml and FSH of 1.25 mIU/ml. Thyroid function was normal (TSH: 1.11 µIU/ml, FT4: 1.56 ng/dl). Leuprolide stimulation was done which suggested central precocious puberty (peak LH: 10.61mIU/ml, peak FSH: 3.75 mIU/ml). MRI of the pituitary hypothalamic area was normal. He was diagnosed to have idiopathic CPP and was initiated on leuprodile depot preparation 3.75 mg intramuscularly once a month. After 6 months, he had grown 5 cm (and basal serum testosterone was still elevated (185.3 ng/dl), LH

Background and aims Malignant transformation of pheochromocytomas/paragangliomas (PCC/PGL) is a rare occurrence, and predictive factors for the same are not well understood. This study aims to identify the predictors of malignancy in patients with PCC/PGL. Materials and methods We performed a retrospective analysis of 142 patients with either PCC or PGL registered at our institute between 2000 and 2015. Records were evaluated for clinical parameters like age, gender, familial/syndromic presentation, symptomatic presentation, biochemistry, size, number and location of tumours and presence of metastases and mode of its diagnosis. Results Twenty patients were found to have metastases; 13 had metastases at diagnosis and seven during follow-up. Metastases were detected by radiology (CT-neck to pelvis) in 11/20 patients (5/13 synchronous and 6/7 metachronous), 131I-metaiodobenzylguanidine in five (2/12 synchronous and 3/6 metachronous) patients and 18F-flurodeoxyglucose PET/CT in 15 (12/12 synchronous and 3/3 metachronous) patients. Malignant tumours were significantly larger than benign tumours (8.3 ± 4.1 cm, range: 3–22 cm vs 5.7 ± 2.3 cm, range: 2–14 cm, P = 0.0001) and less frequently metanephrine secreting. On linear regression analysis, tumour size and lack of metanephrine secretion were the independent predictors of malignancy. Conclusions Patients with primary tumour size >5.7 cm and lack of metanephrine secretory status should be evaluated for possible malignancy not only at diagnosis but also in the postoperative period. As compared to CT and 131I-MIBG scan, 18F-flurodeoxyglucose PET/CT analyses are better (sensitivity: 100%) for the diagnosis of metastases in our study.

Background and Aims: Medical nutrition therapy plays a major role in the management of gestational diabetes mellitus (GDM). However, control of postprandial blood glucose values is often a challenge in Asian Indian GDM women due to high carbohydrate content in Indian diet. Materials and Methods: Women presenting with GDM diagnosis were randomised to high fiber complex carbohydrate diet and soya based protein rich diet (25% of cereal part in the high fiber, complex carbohydrate diet replaced by soya food) groups. Results: At the end of one week after initiation of dietary intervention, patients who received high fiber complex carbohydrate diet (n=30) had significantly higher postprandial blood glucose levels than those who received soya based protein rich diet (n=32). The need for insulin therapy at the end of one week after initiation of dietary intervention (15.62% vs. 40.0%) and at delivery (18.75% vs. 50%) were significantly lower in soya based protein rich diet group. Maternal thyroid function at diagnosis of GDM and delivery and neonatal TSH were not significantly different between the groups. Conclusion: Consumption of soya based protein rich diet reduced the need for insulin therapy in subjects with GDM. Short term consumption of soya food did not alter maternal and neonatal thyroid functions.

Background: Nephrotic syndrome is well-known cause of thyroid dysfunction in children; however, there is limited data on this issue in adults, especially regarding natural course of thyroid abnormalities. Methods: Patients with nondiabetic nephropathies were included in the study and evaluated with thyroid function tests at diagnosis and every 2-3 monthly. Age and sex matched healthy volunteers constituted the control group. Results: The study included 39 patients with newly diagnosed nephrotic syndrome and 39 controls. When compared to the control group, patients with nephrotic syndrome had significantly higher thyroid stimulating hormone and significantly lower total thyroxine, total triiodothyronine, free thyroxine and free triiodothyronine levels. Eighteen patients had remission at last follow-up (18.3±3.4 months) and those with remission had improvement in thyroid function tests. Anti thyroperoxidase antibody tended to be more common in nephrotic syndrome patients and among patients with remission, elevated antibodies was associated with persistence of hypothyroidism. Conclusions: Nephrotic syndrome in adult patients is significantly associated with abnormalities in thyroid function tests. All these abnormalities improve with remission of nephrotic syndrome. Patients with elevated thyroid stimulating hormone and anti-thyroperoxidase antibody levels are more likely to progress to overt hypothyroidism and should be closely followed-up or replaced with levothyroxine.

Background: Hypothyroidism often presents to nephrologists with elevated serum creatinine which may lead to unnecessary evaluation including renal biopsy. Methods: We retrospectively analysed the data of 24 patients who presented to the department of nephrology at our institute with anasarca/facial puffiness or elevated serum creatinine and diagnosed to have hypothyroidism with TSH >40 µIU/ml. Results: Twelve patients presented with generalised edema, eight patients for evaluation of deranged serum creatinine and four patients with both generalised edema and deranged serum creatinine. Age (r=0.696, p

Pheochromocytoma/paraganglioma (PPGL) have been reported to have germline mutations in more than 15 genes. PPGL diagnosed during childhood have the highest heritability (up to 80%). PPGL associated genes are classified into two clusters; cluster 1 (VHL, SDHx, EPAS1, PDH1, PDH2, FH, MDH2) and cluster 2 (RET, NF-1, TMEM127, MAX). Cluster 1 genes associated PPGL are norepinephrine secreting whereas cluster 2 genes associated PPGL are epinephrine secreting. In children with PPGL, VHL mutations are the most common followed by SDHB and SDHD. Bilateral PCC are frequent in patients with VHL mutations whereas extra-adrenal PGL are frequent in SDHx mutations. SDHB related PPGL are frequently malignant. Genetic testing should be performed in all children with PPGL and prioritization of genetic testing based on clinical characteristics (extra-paraganglial manifestations, location and number of PPGL, biochemical phenotype and metastasis) may be cost-effective.How to cite this articleSarathi V, Sabaretnam M, Shah N. Genotype–phenotype Correlation in Children with Pheochromocytoma and Paraganglioma. World J Endoc Surg 2016;8(3):208-211.

Background: Autoimmune hypophysitis is a rare autoimmune endocrinopathy. Literature on natural history of autoimmune hypophysitis is scarce. Methods: We prospectively studied patients with autoimmune hypophysitis between January 2013 to June 2015 and all subjects were followed for at least 6 months. Autoimmune hypophysitis was diagnosed based on clinicoradiologic findings. All patients diagnosed with autoimmune hypophysitis were followed every three monthly with evaluation for pituitary functions and six monthly with gadolinium enhanced MRI of pituitary. Deficient hormones were replaced and none of the patients were treated with immunosuppressive therapy or surgery. Results: Ten cases of autoimmune hypophysitis were diagnosed during the study period. Adrenocorticotropin deficiency was the most common (7/10) followed by thyroid stimulating hormone and gonadotropins (each in 5). Pituitary enlargement and stalk thickening were the most common imaging findings. Three patients had recovery of one hormone in each and none of the patients had progression of mass or new hormone deficiency on follow-up. Conclusions: The study describes natural history of autoimmune hypophysitis in 10 patients from a single center. We suggest against the routine use of immunosuppressive therapy or surgery in patients with autoimmune hypophysitis.

Type 2 diabetes mellitus (T2DM) is associated with a high incidence of vascular disease which can cause significant morbidity and mortality. The risk of cardiovascular mortality in T2DM patients is observed to be more compared to the age-matched subjects. This is attributed to depression of the fibrinolytic system which maintains patency of blood vessels. Endogenous inhibitors such as plasminogen activator inhibitor-1 (PAI-1) inhibit the activation of plasminogen and thus prevent the degradation of fibrinogen. In T2DM there is increased levels of PAI-1. Such a state of altered fibrinolysis is attributed to insulin resistance. A previous study done at our institute demonstrated higher euglobulin lysis time (ELT) in T2DM patients than controls, suggesting altered fibrinolytic activity in the former group. D-dimer is a degradation product of fibrin. Its presence indicates a state of hypercoagulability. In a study by Nwose et al rise in D-dimer levels were observed in diabetics, especially with cardiovascular complications as compared to controls indicating D-dimer could be a useful marker for predicting the complications in T2DM.

Literature on virilising ovarian tumors (VOTs) is limited to case reports and series reporting single pathological type. We have analyzed the clinical, hormonal, radiological, histological, management and outcome data of VOT. This retrospective study was conducted at a tertiary health care center from Western India. Consecutive patients with VOT presenting to our endocrine center between 2002 and 2017 were included. Our study included 13 patients of VOT. Out of 13 patients, two were postmenopausal. All patients in the reproductive age group had secondary amenorrhea except one who presented with primary amenorrhea. Modified F and G score (mFG) at presentation was 24 ± 4.3 and all patients had severe hirsutism (mFG ≥15). Change in voice (n = 11) and clitoromegaly (n = 7) were the other most common virilising symptoms. Duration of symptoms varied from 4 to 48 months. Median serum total testosterone level at presentation was 5.6 ng/mL with severe hyperandrogenemia (serum testosterone ≥2 ng/mL) but unsuppressed gonadotropins in all patients. Transabdominal ultrasonography (TAS) detected VOT in all except one. Ten patients underwent unilateral salpingo-oophorectomy whereas three patients (peri- or postmenopausal) underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Seven patients had Sertoli Leydig cell tumor, three had steroid cell tumor and two had Leydig cell tumor and one had miscellaneous sex cord stromal tumor. All patients had normalization of serum testosterone after tumor excision. In conclusion, VOTs present with severe hyperandrogenism and hyperandrogenemia. Sertoli Leydig cell tumor is the most common histological subtype. Surgery is the treatment of choice with good surgical outcome.

The differential diagnosis of a girl presenting with primary amenorrhoea includes numerous conditions. Often, patients of 46XY disorder of sex development (DSD) are reared as girl and present with primary amenorrhoea. Their further evaluation to reach the final diagnosis is often a great challenge. In this article, we report a challenging case of 46XY DSD presented with primary amenorrhoea. Patient had spontaneous breast development which initially confused the diagnosis to complete androgen insensitivity syndrome. However, low testosterone suggested against this possibility and further evaluation revealed hormonal findings consistent with 17α hydroxylase/17,20 lyase (CYP17A1) deficiency. Patient had 46XY karyotype and in consistence with hormonal findings patient was found to have a likely pathogenic homozygous c.1345C>T (p.Arg449Cys) variation in exon 8 of CYP17A1.

Employees are important assets of an Organization. A successful organization needs to consider employees’ careers, skill sets and opportunities for them to grow in different domains while aligning with its long-term vision. An organization should be able to provide ample career choices for their employees. Also, the employees should be given the liberty to choose from possible career options provided by the organization. The proposed solution involves the formation of an Analytical model to address these concerns in terms of: A. Organization: i) to predict skill set gaps of its employees for upcoming and current designations, ii) ensure organization's vision is aligned with employee's skills, iii) create opportunities for employees to explore different career options with their current skills, iv) forecast attrition and assist in internal job requisitions. B. Employee: i) to visualize career transitions and explore different career opportunities, ii) recommend skills and trainings to acquire those skills for job roles in new business areas. The solution represents attributes for designations, skills and job profile of employees for an organization based on career history that serves as data set for user-based collaborative filtering, hence recommendations can be provided for Employees and Organization. This model will improve the employee's engagement within the organization, helps to reduce the probable attritions and foster a culture of trust. Organizations can effectively understand their employees. Employees can anticipate their careers.